A review on fish‐borne zoonotic parasites in Iran

Abstract Background Fish is a great nutritious food and provides quality protein and a variety of vitamins and minerals. This contributes significantly to the economy and food security in Iran. However, there are safety concerns related to the presence of zoonotic parasites. Objectives The objective of this study is, therefore, to review fish‐borne zoonotic parasites in Iran. Methods Keywords such as fish‐borne, parasites, zoonotic, Iran, and some names of fish‐borne zoonotic parasites were searched in databases including PubMed, Science Direct, Elsevier, SID, Magiran, Irandoc, Google Scholar and the World Health Organization. Results The most common fish‐borne parasites with zoonotic potential identified in reports in the literature were the protozoa Balantidium spp., Myxobolus spp. and Sarcosystis sp.; the trematodes Heterophyes heterophyes and Clinostomum complanatum; the cestodes Ligula intestinalis and Diphyllobothrium latum; the nematodes Pseudoterranova sp., Anisakis spp., Contracaecum spp., Raphidascaris spp., Eustrongylides spp. and Capillaria sp.; and the acanthocephal Corynosoma spp. Conclusions The potential risk factors for the transmission of fish‐borne zoonotic parasites to humans are consumption of raw or undercooked infected fish, contact with contaminated water and contact with infected fish. There is a need for epidemiological surveillance of fish for parasites with zoonotic potential and of occurrence of infections in humans to better understand the public health significance and design prevention programs.

of raw or inadequately cooked fish can be a major public health concern due to is fish-borne zoonotic parasites (FBZPs) .
Consumption of raw fish such as sushi and sashimi, commonly found in Japan's national dishes, as well as the culinary tradition of consumption of marinated or raw fish in European countries such as Italy are a significant source of human infections with FBZP (Yorimitsu et al., 2013). The World Health Organization (WHO) estimates approximately 56 million cases of parasite infections associated with the consumption of raw or undercooked fish or fish products but worldwide the number of people at risk, including those in developed countries, is more than half a billion (Santos & Howgate, 2011;WHO, 1995WHO, , 2004WHO, , 2012. Recent official statistics suggest that approximately 1.5 million people in Korea, 6 million people in China and over 5 million in Thailand are infected with FBZPs including liver flukes such as Clonorchis sinensis and Opisthorchis viverrini Chai, 2005).
In developed countries, people usually have information about meat-borne zoonosis such as trichinellosis and cysticercosis, while far fewer are acquainted with fish-borne parasitic zoonoses like opisthorchiasis, intestinal trematodiasis, anisakiasis or diphyllobothriasis. Yet these zoonotic parasites from fish are responsible for large numbers of human infections . Although epidemiological data are scarce, the prevalence and species diversity of FBZPs in Iran suggest that these parasites are also an important national public health problem (Pazooki & Masoumian, 2012;Rahmati et al., 2020).
The main goals of this paper are to describe the most important parasitic hazards present in fish meat in Iran, to bring attention to the need for epidemiological studies on fish infections and human infections with zoonotic parasites and to highlight the need for increased public awareness concerning the risks of consuming incorrectly prepared fish meat.

METHODS
A systematic review of the literature was performed using online databases from various fields and in Iran from 1981 to 2020. Databases

Impacts
• The potential risk factors for fish-borne parasitic zoonoses are consumption of raw infected fish and fish products and contact with contaminated water or infected fish. • The presence of zoonotic parasites in fish in Iran could impose a potential risk to human health.
• It was documented that among the pathogenic parasites infecting fish, majority of them are zoonotic and the most common fish-borne zoonotic parasites were the protozoa, trematodes, cestodes and nematodes performed and study area(s). All data were summarised in tabular form (Tables 1-5).

FISH-BORNE ZOONOTIC PARASITES
A total of 200 documents were obtained with references to FBZPs in Iran. These result show that many studies have been conducted on the parasitic infections of fish in Iran; however, from the point of view of fish parasites with zoonotic potential, there is no comprehensive review with many studies focused on individual fish species or parasites. During this study, according to the available data, 58 species of zoonotic parasites were recorded from 112 fish species, from different faunal regions. Protozoa had the most parasites (36 species) followed by nematodes, trematodes, cestodes and acanthocephalan 16, 2, 2 and 2 different species of parasites, respectively.

Fish-borne zoonotic protozoa
Three protozoa in fish were identified in the literature, Balantidium and Sarcocystis, with the first in Barbus sharpeyi, Barbus grypus and Ctenopharyngodon idella and the latter only in B. sharpeyi.

Balantidium spp
The genus Balantidium has a large number of species that have been reported in the digestive tracts of a widely diverse range of invertebrate and vertebrate hosts such as molluscs, arthropods, fish, amphibians, reptiles, birds and mammals including humans (Biswas & Mukherjee, 1981;Bradbury, 1994aBradbury, , 1994bLi et al., 2008Li et al., , 2014 been reported in freshwater fish, eight of which have been described in China and two of which (Balantidium ctenopharyngodoni and B. polyvacuolum) are reported most frequently (Chen, 1955;Li, 1963;Li et al., 2014;Zhao & Ma, 1992). Four species have been reported in marine fish with Balantidium prionurium reported more commonly particularly in surgeonfish (Prionurus punctatus) (Norman Grim, 1985).
Data collected from different regions of Iran showed that this parasite was found in two species of fish (Barbus sharpeyi and Barbus grypus) from Shadegan and Sosangerd city and Khouzestan Province (Rahdar et al., 2012;Seyed Mortezaei et al., 2008) (Table 1).

Sarcosystis
For the more than 150 species of Sarcocystis, most intermediate hosts include herbivorous mammals and humans and other primates but also some birds, reptiles and possibly fish. Definitive hosts include carnivores or omnivores, including humans and some reptiles and raptorial birds (Fayer et al., 2015).  (Rosenthal et al., 2012). Symptoms in humans can include nausea, vomiting and enteritis (acute, chronic and severe) (Fayer et al., 2015).
The clinical significance of Sarcocystis in fish as well as the role of fish in contributing to zoonosis are not well understood. Most reports in fish have been in trout. The first report of Sarcocystis infection (15%) in muscles of Barbus sharpeyi from Shadegan and Susangerd city, Iran was by Rahdar et al. (2012). They suggested that consumption of raw or under cooked fish in the endemic region be avoided (Table 1).

Myxobolus spp
Myxozoans are economically important group of microscopic metazoan parasites, which cause disease in a large variety of commercially important fishes. They have also been reported in platyhelminthes, reptiles, amphibians, mammals as well as in faecal sample of human beings (Boreham et al., 1998

Heterophyes heterophyes
Heterophyes heterophyes is a small parasitic fluke that infects humans who eat raw or undercooked fish infected with the metacercaria stage of the parasite. A variety of mammals (e.g., dogs, foxes and jackals) other than humans take the role of reservoir hosts (Chai, 2007 H. heterophyes is commonly found in the Middle East, Philippines, Taiwan, Korea, China and Japan (Chai, 2007;Yu et al., 1994). Massoud et al. (1981) showed that the rate of infection with H. heterophyes in man and carnivores in Khuzestan, Iran was 8% and 9.5% respectively (Massoud et al., 1981). Farahnak (2001) identified a prevalence of 1.9% in people of Mazreeh district in Khouzestan Province, Iran (Farahnak, 2001). Carnivores, particularly golden jackals, foxes and dogs serve as the main natural reservoir host for heterophyid infection in the Khuzcstan area, Iran. These animals frequently feed on frogs, brackish-water fish, snails and other small creatures in the area and contaminate the water bodies with their faeces, so that aquatic snails become infected and transmission continues. Prevalence in fish in Iran has not been determined.

Clinostomum complanatum
Clinostomum complanatum is a digenetic trematode, which usually infects birds after consuming infected fish or amphibians. Metacercariae of C. complanatum are often yellow and encyst in a variety of sites in the body such as the oral cavity, gills, intestines, tail, muscles and eye sockets of fish or amphibians, causing 'yellow grub disease' . According to previous epidemiological studies, 12 species of freshwater fish were recorded as the second intermediate hosts (Chung et al., 1995;Rim et al., 1996), and one species of freshwater snail (Species) was reported as the first intermediate host of C. complanatum (Chung et al., 1998). If a human consumes an infected raw fish, the fluke can attach to the surface of the mucus membrane of the throat and cause a clinical syndrome called halzoun. Several reports are available on the occurrence of C. complanatum in Iranian freshwater fish in different areas of Iran. The results showed that the highest infection with C. complanatum (61.4% and 28%) is observed in gill cavities, gill arches, operculum, muscles and fins of Capoeta capoeta gracilis from Shirood River, Mazandaran (Ghazifard et al., 2011;Roohi & Malek, 2005). Infection with C. complanatum has been observed in several other fish species in Iran with prevalence ranging from 3% to 16.6% (Table 2). This difference may be due to the climatic conditions of the study area, species, length and habitat (lentic or semi-lotic) of the host fish (Dias et al., 2006). Dias et al. (2006) showed that there are host fish preferences and a strong and positive effect of the host length upon the prevalence, that is, the larger the fish, the higher the probability of being infected (Dias et al., 2006).
Given the prevalence of C. complanatum and variety of fish infected, prevalence studies in humans are needed and awareness of halzoun increased.

Ligula intestinalis
Ligula intestinalis is a cestode from the family pseudophilidae, which are three-host parasites. It infects a range of fish species and is found in free living and farmed fish all over the world (Scholz et al., 2003) and there are several reports of human infestations with this parasite (Urdes & Hangan, 2013 and Alburnoides biponctatus (80%) (Mortazavi et al., 2005) (Table 3).
The difference in the prevalence of this parasite in different regions of Iran is attributed to the ecosystem of the region. In basins such as Vahdat, Aras, Sattar Khan and Zayandehrud dams compared to Gorganrood and Algol, which have more water, there is a larger population of fish-eating birds, which play an important role in the spread of this parasite (Mazandarani et al., 2018). In contrast to trematodes such as C. complanatum, the prevalence of L. intestinalis decreases with increasing fish size, probably due to selective mortality among parasitised individuals (Garedaghi & Mohammadi, 2012;Mortazavi et al., 2005 Human infection with D. latum is acquired by eating uncooked freshwater fish containing the parasite's plerocercoid cysts (Dick, 2007).

Pseudoterranova spp
Pseudoterranova is a genus of parasitic nematodes within the family Anisakidae. The lifecycle of Pseudoterranova spp. involves marine mammals such as sea lions, seals and walruses as final hosts (Hochberg et al., 2010) and planktonic or benthic crustaceans as intermediate hosts.
Fish are a second intermediate or paratenic host (Brunet et al., 2017).
In some regions, increasing seal numbers have prefaced an increase in fish infected with P. decipiens (Lunneryd et al., 2015). Pseudoterranova, which is found in wild caught and farmed fish, can impact the health and swimming ability of infected fish, resulting in mortality (Buchmann & Mehrdana, 2016). Species belonging to this genus also can adversely impact human health with exposure occurring via the consumption of raw or under cooked infected fish (Shamsi & Sheorey, 2018;. Cases of human infection have been reported from consuming partially cooked fish infected with P. decipiens (Shamsi, 2019), P.
Pseudoterranova was detected from Saurida tumbil (25%) and Tylosurus crocodilus crocodile (14.28%) in the Persian Gulf, Iran by Dadar et al. (2016). In a study by Hosseini et al. (2013), this parasite was found in the stomach of Psettodes erumei from the Persian Gulf with a prevalence of 4.1% (Hosseini et al., 2013). The species of this parasite infecting fish from Iran needs to be determined to better understand the health risk to fish and people.

Anisakis spp
Anisakiasis is the zoonotic disease triggered by the third stage larvae of the nematodes, Anisakis (Nieuwenhuizen & Lopata, 2013). This parasite habitually infects adult marine mammals. Intermediate and/or paratenic hosts include crustaceans, cephalopods and fish (Nieuwenhuizen & Lopata, 2013). Humans are accidentally infected via the ingestion of raw or inadequately cooked or fish and shellfish (Aibinu et al., 2019). Symptoms of acute anisakiasis include severe abdominal pain, nausea and vomiting. Some of these symptoms closely mimic peptic ulcer, appendicitis or peritonitis with the most concerning presentation being allergic sensitisation, which is usually serious and ranges from urticaria to anaphylactic shock (Villazanakretzer et al., 2016).
Anisakis simplex, the primary zoonotic species, was believed to occur mainly in spotted chub mackerel (Scomber japanicus) and Japanese flying squid (Todarodes pacificus) (Nagasawa & Moravec, 1995). However, more recently, Abollo et al. (2001) concluded that most species of cephalopods and fish can potentially harbour these marine parasitic nematodes as 200 fish and 25 cephalopods species have been identified as hosts for Anisakis.
In Iran, the highest and lowest rate of infection with Anisakis spp.
In many studies conducted in Iran, the species of Anisakis has not been determined; to better understand risk of human infection, more spe-  (Anderson, 2000).
Contracaecum spp. larvae can infect humans with the disease referred to as anisakiasis, the same name as used to refer to disease caused by Anisakis spp. As with Anisakis spp., infection in humans with Contracaecum spp. occurs via the consumption of raw or undercooked fish which are host to the third stage larvae. The symptoms of anisakiasis include abdominal pain and distention, diarrhoea with blood and mucus, nausea and a mild fever. There can also be allergic reactions such as rash and itching, and occasionally there can also be anaphylaxis (Ivanović et al., 2017).
The first report of Contracaecum osculatum baicalensis in Iran was by Eslami et al. (1972) who documented the parasite in the gastrointestinal tract of pike (Esox lucius; from the Caspian Sea with a prevalence of 36.7%) (Eslami et al., 1972). In subsequent studies, Contracaecum squalii was found in acipenseridae fish (Mokhayer, 1974). Contracaecum spp. have now been recorded from several fish species in Iran (Table 4).  (Jahantab et al., 2014). There are some reports on its zoonotic importance (Doupé et al., 2003), but according to Cheng (1998) since the adults of Raphidascaris are intestinal parasites of fish, it is doubtful whether they can cause human infection (Cheng, 1998). However, the collected data showed that this parasite was isolated from freshwater fish in Iran with a prevalence of 0.5% in Rutilus frisii kutum to 86.05% in Silurus glanis (Daghigh Roohi & Satari, 2004

Hysterothylacium spp
Hysterothylacium is a genus of parasitic roundworms in the family raphidascarididae. As of 2020 it contains of over 70 species and is considered one of the largest of the ascaridoid genera parasitising fish (Ghadam et al., 2018;Li et al., 2007;Shamsi, 2017). The life cycle involves predatory teleost fish as the final host and various species of invertebrates and teleost as the intermediate hosts (Deardorff & Overstreet, 1980 (Branciari et al., 2016;Ljubojevic et al., 2015a). Some of the more commonly infected fish species include Neogobius fluviatilis, N. kessleri, N.

Corynosoma strumosum are common in commercial fish species in
Iran (Sasaki et al., 2019). The highest prevalence of infection with C.

CONCLUSION
Changes in food habits/tastes in recent years have led to an increase in the consumption of raw fish and less cooked fish products and this new tendency has increased the risk of exposure of the consumer to parasitic hazards. In conclusion, this review revealed that some of the fish-borne zoonotic parasites are common in different freshwater fish species mainly Barbus spp., Capoeta spp., Cyprinus spp. and and protozoa (Balantidium spp. and Sarcosystis sp.).
Despite the fact that fish-borne parasitic zoonosis due to the culture and food habits in Iran and the lack of consumption of raw fish products has not been reported, but due to eating raw or undercooked meat of infected fish or contact with contaminated water or infected fish cause human infection, so control methods such as complete cooking of fish meat and avoiding contact with potentially contaminated water are suggested. Awareness-raising activities should also be conducted on the nature of fish-borne zoonotic parasites and the risk of consuming raw fish.

ACKNOWLEDGEMENTS
This study was supported by the University of Tabriz. We would like to thank all participants of this outbreak investigation for their contribution to these findings. Moreover, the authors would like to acknowledge all staff members of Veterinary Parasitology Laboratory of University of Tabriz.

CONFLICT OF INTEREST
There is no conflict of interest.

DATA AVAILABILITY STATEMENT
Research data are not shared.

ETHICAL STATEMENT
Systematic reviews generally do not need ethics committee or institutional review board approval.